The goal of this program-project is to better understand how the microcirculation creates and maintains an appropriate environment for the parenchymal cells. To achieve this goal we will study the fundamental processes of regulation and exchange in the microcirculation and certain inter-relationships between these two functions. A significant portion of the effort will be devoted to examining the behavior or individual microcirculatory vessels as well as the organized networks which they comprise. We will also examine the manner in which oxygen is delivered by the microcirculatory system to the parenchymal cells and the variations in tissue metabolism and oxygen delivery under different circumstances. We will also study the nature of the exchange barriers in the microcirculation for lipid-insoluble substances and the effect of these barriers in the microcirculation for lipid-insoluble substances and the effect of these barriers on the environment of the parenchymal cells. The program-project is being expanded substantially to add new studies on the function of the microcirculation at the cellular level. These studies are made possible by technical developments which enable us to examine questions of continuing interest to this project with new methods. By examining microcirculatory function at several levels as well as the interrelationships among separate functions we aim to achieve a better understanding of the manner in which the microcirculation supports normal parenchymal cell function. One of the distinguishing features of this program-project is the interdisciplinary nature of the research. The group has special expertise in the areas of physiology, engineering, applied mathematics, morphology and cell biology. At least two of these disciplines are represented in the typical project in the program-project. While the emphasis in the program is on the advancement of scientific understanding, we recognize that scientific advances are very dependent upon technological developments. Therefore, a portion of the activities of the program are directed to development of new instrumentation.